Nitric Oxide in Gastroprotective and Ulcer Healing Effects of Sucralfate

Abstract

Background: Sucralfate is known to protect gastric mucosa against the damaging action of strong irritants and to accelerate healing of chronic ulcers, but the mechanisms underlying these effects have not been elucidated. Similar gastroprotective and healing effects can be obtained with exogenous donors of nitric oxide (NO) and prostaglandins (PG). Methods: The area of gastric lesions was measured by planimetry. Gastric blood flow was determined using laser Doppler flowmetry. The role of NO in the prevention of ethanol-induced gastric damage and in the healing of gastric ulcerations by sucralfate and nocloprost, a stable PGE₂ analog, was therefore assessed. Results: Pretreatment with N^G-nitro-l-arginine (l-NNA), an inhibitor of NO synthase, enhanced ethanol-induced mucosal damage and reduced dose-dependently the gastroprotective and hyperemic effects of sucralfate. The doses of l-NNA attenuating significantly the protective effects of sucralfate were 25–50 mg/kg. The effects of l-NNA were reversed by the addition of l-arginine but not d-arginine. For comparison, the gastroprotective (but not hyperemic) effects of nocloprost were not affected by the pretreatment with l-NNA and/or arginine. Daily treatment with l-NNA (50 mg/kg per day) prolonged the healing of chronic gastric ulcers and significantly reduced the acceleration of healing by sucralfate. Conclusions: We conclude that (i) the gastroprotective and hyperemic effects of sucralfate involve, at least in part, the NO-arginine pathway, (ii) the ulcer healing effects of sucralfate may also involve NO, probably through the hyperemia around the ulcer, and (iii) NO is not essential for the mucosal protection of PGE₂ analog, but may account for the gastric vasodilatory effect of this PG.

Key Words:

• Mucosal blood flow
• nitric oxide
• prostaglandins
• protection
• stomach
• ulcer healing